Cyclopropane skeleton monophosphine ligand as well as preparation method and application thereof

Abstract

The invention belongs to the field of metal complex catalysts, and relates to a cyclopropane skeleton monophosphine ligand as well as a preparation method and application thereof. The cyclopropane skeleton monophosphine ligand has the following structural formula: # imgabs0 #, wherein R1 is phenyl, substituted phenyl, C1-C8 alkyl and C1-C8 alkoxy, R2 is phenyl, substituted phenyl and C1-C8 alkyl, and R1 and R2 are the same or different. The cyclopropane skeleton monophosphine ligand disclosed by the invention can be conveniently prepared from easily available raw materials through simple conversion. The complex of the cyclopropane skeleton monophosphine ligand and palladium can be used as a catalyst for C-N coupling reaction and Suzuki coupling reaction, shows very high catalytic activity and has a very good application prospect.

Description

Technical Field

[0001] The invention belongs to the field of metal complex catalysts, in particular to a type of cyclopropane skeleton monophosphine ligand, a preparation method and application thereof. Background Art

[0002] In metal complex catalysts, ligands can adjust the electrical properties and steric hindrance of the center, thereby affecting the activity and selectivity of the catalyst. Therefore, the development of new ligands is an important research topic in the field of metal complex catalysis.

[0003] Monophosphine ligands are an important class of ligands. On the one hand, as a soft Lewis base, they can coordinate with most low-valent transition metals. On the other hand, they can coordinate with metal centers flexibly in a mono-, di- or even multi-coordinated manner. Therefore, monophosphine ligands are widely used in metal complex catalysis. For example, people have successfully used monophosphine ligands in palladium-catalyzed CN coupling reactions and CC coupling reactions. The skeleton of the monophosphine ligand significantly affects the catalytic performance of the corresponding metal complex catalyst. For example, monophosphine ligands with a cyclic aromatic skeleton usually show unique advantages in CN coupling reactions. [Ruiz-Castillo, P.; Buchwald, SL Chem. Rev. 2016, 116, 12564]. However, the monophosphine ligands with a cyclic aromatic skeleton are too rigid, and the amount of palladium catalyst added still needs to be increased for the coupling of some amines such as nitrogen-containing heterocycles and diarylamines. Therefore, the development of monophosphine ligands with new skeletons is expected to improve the activity of its metal complex catalysis and even regulate its selectivity, which has important theoretical and practical significance. Summary of the invention

[0004] The purpose of the present invention is to provide a cyclopropane skeleton monophosphine ligand, a preparation method and application thereof, so as to overcome the shortcomings of the prior art.

[0005] The present invention relates to a cyclopropane skeleton monophosphine ligand, a preparation method and an application thereof. Specifically, starting from trans-1,2-diarylethene, a cyclopropane skeleton monophosphine ligand having 2,3-trans-diaryl substitution is synthesized through cyclopropanation reaction, debromination reaction, substitution reaction and other steps, wherein two trans-aryl groups are ortho-substituted aryl groups. The complex of the cyclopropane skeleton monophosphine ligand and palladium can efficiently catalyze CN bond coupling reaction and Suzuki coupling reaction, and has good application prospects.

[0006] The first aspect of the present invention is to provide a cyclopropane skeleton monophosphine ligand I (named T-Phos) having the following structural formula:

[0007]

[0008] in:

[0009] R 1 is phenyl, substituted phenyl, C1-C8 alkyl, C1-C8 alkoxy, R 2 is phenyl, substituted phenyl, C1-C8 alkyl, R 1 , R 2 It can be the same or different;

[0010] The substituents in the substituted phenyl are one or more of C1-C8 alkyl, C1-C8 alkoxy, C2-C8 acyloxy, hydroxy, halogen, amino, (C1-C8 acyl)amino, di(C1-C8 alkyl)amino, C1-C8 acyl, C2-C8 ester, and alkyl halide; the number of substituents is 0-5;

[0011] The C1-C8 alkyl group is methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, sec-pentyl, tert-pentyl, n-hexyl, isohexyl, neohexyl, sec-hexyl, tert-hexyl, n-heptyl, isoheptyl, neoheptyl, sec-heptyl, tert-heptyl, n-octyl, isooctyl, neooctyl, sec-octyl or tert-octyl;

[0012] The C1-C8 alkoxy group is methoxy, ethoxy, propoxy, n-butoxy, isobutoxy, n-pentyloxy, isopentyloxy, sec-pentyloxy, neopentyloxy, n-hexyloxy, isohexyloxy, neohexyloxy, sec-hexyloxy, n-heptyloxy, isoheptyloxy, neoheptyloxy, sec-heptyloxy, n-octyloxy, isooctyloxy, neooctyloxy, sec-octyloxy, 1-cyclopropylmethoxy, 1-cyclobutylmethoxy, 1-cyclopentylmethoxy, 1-cyclohexylmethoxy, 1-cycloheptylmethoxy;

[0013] Preferably, the cyclopropane skeleton monophosphine ligand is:

[0014]

[0015] The above-mentioned cyclopropane monophosphine ligand I can react with borane to generate a more stable borane adduct II of the cyclopropane monophosphine ligand, which is convenient for use and storage.

[0016]

[0017] The second aspect of the present invention provides a method for preparing a cyclopropane skeleton monophosphine ligand I and its borane adduct II, comprising the following steps:

[0018] (1) Using 1-10 equivalents of NaOH as a base and 0.1-0.5 equivalents of benzyltriethylammonium chloride (TEBAC) as a phase transfer catalyst, trans-1,2-diarylethene and a solvent amount of bromoform are subjected to a cyclopropanation reaction to prepare a gem-dibromocyclopropane intermediate III, the reaction formula of which is:

[0019]

[0020] Where R 1 As defined for Compound I.

[0021] (2) In a mixed solvent of tetrahydrofuran and diethyl ether, 1-2 equivalents of LiBr are used as an additive, and 1-1.5 equivalents of n-butyl lithium are exchanged with the gem-dibromocyclopropane intermediate III at -78°C to -100°C. After the reaction is complete, the monobromocyclopropane intermediate IV is prepared by quenching with methanol. The reaction formula is:

[0022]

[0023] Where R 1 As defined for Compound I.

[0024] (3) In tetrahydrofuran, 1-1.5 equivalents of n-butyl lithium are exchanged with monobromocyclopropane intermediate IV at -78°C to -100°C. After the reaction is completed, 2-4 equivalents of PR are added. 2 2Cl, the system is naturally heated to room temperature and then stirred until the reaction is complete to obtain cyclopropane monophosphine ligand I; if the ligand is highly stable, it can be directly separated and purified; if the ligand is less stable, the system can be cooled to 0°C and then borane tetrahydrofuran solution can be added, and then the temperature is restored to room temperature and the reaction is continued until complete to obtain cyclopropane skeleton monophosphine ligand borane adduct II, the reaction formula of which is:

[0025]

[0026] Among them, R 1 -R 2 As defined for Compound I.

[0027] Furthermore, a method for preparing a free phosphine ligand I from a monophosphine ligand borane adduct II of a cyclopropane skeleton by deborane protection is as follows:

[0028] At 50-90°C, 1,4-diazabicyclo[2.2.2]octane (DABCO) removes the borane of the cyclopropane skeleton monophosphine ligand borane adduct II to obtain the cyclopropane skeleton monophosphine ligand I, and the reaction formula is:

[0029]

[0030] The third aspect of the present invention provides the use of a complex of a cyclopropane skeleton monophosphine ligand and palladium as a catalyst to promote CN coupling reaction.

[0031]

[0032] Where: Ar 1is phenyl, substituted phenyl, heteroaryl, or alkenyl; R 3 and R 4 is phenyl, substituted phenyl, C1-C8 alkyl, R 3 , R 4 They may be the same or different; X is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

[0033] The substituted phenyl group is a phenyl group substituted with an alkyl group, an aryl group or a heteroatom at positions 2 to 6. Preferably, the phenyl group is substituted with an alkyl group at positions 2 to 6. More preferably, the phenyl group is o-tolyl, m-tolyl, p-tolyl, mesityl, mesityl and unityl.

[0034] The heteroaryl group is pyridyl, thienyl, furyl, pyrrolyl, pyranyl, pyrazolyl, piperonyl, preferably pyridyl, thienyl, furyl, piperonyl, more preferably furyl, piperonyl.

[0035] The alkenyl group is a C1-C8 straight chain or branched alkenyl group, preferably a C1-C8 straight chain alkenyl group, and more preferably vinyl, propenyl, or butenyl.

[0036] The C1-C8 alkyl group is a C1-C8 straight-chain alkyl group, preferably a C3-C6 straight-chain alkyl group, and more preferably n-propyl, isopropyl, and n-butyl.

[0037] The fourth aspect of the present invention provides the use of a complex of a cyclopropane skeleton monophosphine ligand and palladium as a catalyst to promote the Suzuki coupling reaction.

[0038]

[0039] Where: Ar 2 ,Ar 3 is phenyl, substituted phenyl, heteroaryl, alkenyl, Ar 2 ,Ar 3 They may be the same or different; X is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

[0040] The substituted phenyl group is a phenyl group substituted with an alkyl group, an aryl group or a heteroatom at positions 2 to 6. Preferably, the phenyl group is substituted with an alkyl group at positions 2 to 6. More preferably, the phenyl group is o-tolyl, m-tolyl, p-tolyl, mesityl, mesityl and unityl.

[0041] The heteroaryl group is pyridyl, thienyl, furyl, pyrrolyl, pyranyl, pyrazolyl, piperonyl, preferably pyridyl, thienyl, furyl, piperonyl, more preferably furyl, piperonyl.

[0042] The alkenyl group is a C1-C8 straight chain or branched alkenyl group, preferably a C1-C8 straight chain alkenyl group, and more preferably vinyl, propenyl, or butenyl.

[0043] Advantages and beneficial effects of the present invention:

[0044] The cyclopropane skeleton monophosphine ligand of the present invention can be conveniently prepared from readily available raw materials through simple conversion. The complex of the cyclopropane skeleton monophosphine ligand and palladium can be used as a catalyst for CN coupling reaction and Suzuki coupling reaction, exhibits high catalytic activity, and has good application prospects. DETAILED DESCRIPTION

[0045] The following embodiments will help to further understand the present invention, but it should not be understood that the scope of the above subject matter of the present invention is limited to the following embodiments. All technologies realized based on the above content of the present invention belong to the scope of the present invention.

[0046] General Notes:

[0047] The abbreviations used in the following examples have the following meanings:

[0048] Me is methyl, Et is ethyl, t Bu is not tert-butyl, n Bu is n-butyl, Ph is phenyl, THF is tetrahydrofuran, Et2O is diethyl ether, CHBr3 is bromoform, TEBAC is benzyltriethylammonium chloride, PE is petroleum ether, EA is ethyl acetate, Ar is argon, CDCl3 is deuterated chloroform, COD is 1,5-cyclooctadiene, and TMS is a trimethylsilane substituent.

[0049] eq. is equivalent, rt stands for room temperature, S / C is the ratio of the amount of substance of substrate to catalyst, ND stands for not detected, TLC is thin layer chromatography, NMR is nuclear magnetic resonance, HRMS is high resolution mass spectrometry, GC is gas chromatography, conversion rate = amount of substance of converted raw material / amount of substance of starting raw material, conversion number = amount of substance of target product / amount of substance of catalyst.

[0050] The solvents used were purified and dried by standard operation before use; the reagents used were commercially available or synthesized according to existing literature methods and purified before use.

[0051] Examples 1-4 are preparation examples, and Examples 5-10 are application examples.

[0052] Example 1: Synthesis of 2,3-di(o-methylphenyl)cyclopropyldi-tert-butylphosphine borane adduct II-a:

[0053] Step 1: Synthesis of 2,3-di(o-methylphenyl)-1,1-dibromocyclopropane III-a:

[0054]

[0055] (E)-1,2-di-o-methylstyrene (8.3 g, 40 mmol), benzyltriethylammonium chloride (TEBAC, 1.83 g, 8 mmol, 20 mol%) and CHBr3 (80 mL) were added to a 250 mL three-necked flask. The obtained reaction mixture was degassed by freezing three times, replaced with an argon atmosphere, placed in an oil bath, and heated to 95 ° C until the reaction was completed. After the reaction was completed by TLC monitoring, it was washed with saturated NH4Cl (aq., 50 mL), and the organic phase was extracted with DCM (100 mL × 3). The organic phases were combined, dried over anhydrous MgSO4, filtered, and the filtrate was concentrated by rotary evaporation. The crude product was separated by silica gel column chromatography (eluent: petroleum ether ~ petroleum ether / ethyl acetate = 100: 1) to obtain the target product III-a as a white solid with a yield of 89% and a melting point of 213-214 ° C.

[0056] 1 H NMR (400MHz, CDCl3) δ7.31–7.25(m,4H),7.20–7.16(m,2H),7.13(m,2H),3.15(s,2H),2.53(s,6H).

[0057] 13 C NMR (101MHz, CDCl3) δ139.28,135.63,130.16,128.14,127.81,126.09,39.62,36.98,20.40.

[0058] HRMS(ESI) Calculate for [M+H,C 17 H 18 Br2] + :378.9697,found:378.9698.

[0059] Step 2: Synthesis of 2,3-di(o-methylphenyl)-1-bromocyclopropane IV-a:

[0060]

[0061] In a glove box, lithium bromide (104 mg, 1.2 mmol) was weighed into a 50 mL Schlenk bottle A equipped with an electromagnetic stirrer, and 10 mL of anhydrous ether and 10 mL of anhydrous tetrahydrofuran were added. Reactant III-a (378 mg, 1 mmol) was weighed into another 50 mL Schlenk bottle B and dissolved in 10 mL of anhydrous tetrahydrofuran. Both were taken out of the glove box, and n-BuLi in n-hexane solution (0.5 mL, 2.4 M, 1.2 mmol) was added to A at -100 ° C. After half an hour, the solution in B was added dropwise, and the dripping was completed in 1 hour, and then kept stirring at low temperature for 1 hour. After the reaction was completed by TLC monitoring, 2 mL of methanol was added to the system to quench, silica gel was added to mix the sample, and column chromatography was separated (eluent: petroleum ether~petroleum ether / ethyl acetate=100:1) to obtain the target product Iv-a as a yellow liquid with a yield of 51%.

[0062] 1 H NMR (400MHz, CDCl3) δ7.29–7.11(m,8H),3.44(ddd,J=7.9,4.3,1.9Hz,1H),2.83(dt,J=6.0,2.3Hz,1H),2.65–2.60(m,1H),2.50(s,3H),2.40(s,3H).

[0063] 13 C NMR (101MHz, CDCl3) δ138.73,138.42,137.68,135.63,130.22,130.02,128.68 ,127.45,127.22,126.43,126.20,125.85,30.4,30.1,29.6,20.30,19.90.

[0064] HRMS(ESI) Calculate for [M+H,C 17 H 18 Br] + :301.0592,found:301.0591.

[0065] Step 3: Synthesis of 2,3-di(o-methylphenyl)cyclopropyldi-tert-butylphosphine borane adduct II-a:

[0066]

[0067] Reactant IV-a (300 mg, 1 mmol) was weighed into a 50 mL Schlenk bottle equipped with electromagnetic stirring, dissolved in anhydrous tetrahydrofuran under argon atmosphere, and n-BuLi n-hexane solution (0.5 mL, 2.5 M, 1.2 mmol) was added dropwise at -100 °C, and stirred at low temperature for 1 hour.t Bu2Cl (361mg, 2mmol), the reaction system is naturally warmed to room temperature and stirred for 4 hours. After the reaction is completed by TLC monitoring, the temperature is controlled by ice water bath (0℃), and borane tetrahydrofuran solution (4mL, 1.0M, 4mmol) is added to the system, and the system is restored to room temperature and stirred for 12 hours. The temperature system is controlled by ice water bath, and water is added dropwise to quench the reaction system, and 10mL of ethyl acetate is extracted three times, the organic phases are combined, dried with anhydrous MgSO4, filtered, and the filtrate is concentrated by rotary evaporation. The crude product is separated by silica gel column chromatography (eluent: petroleum ether~petroleum ether / ethyl acetate=100:1) to obtain the target product II-a as a white solid with a yield of 59% and a melting point of 162-163℃.

[0068] 1 H NMR (400MHz, CDCl3) δ7.56(d,J=7.7Hz,1H),7.25–7.06(m,6H),6.98–6.93(m,1H),3.49(dt,J=12.2,7.2Hz,1H), 2.53(m,4H),2.41(s,3H),1.93(ddd,J=9.5,6.9,4.8Hz,1H),1.23(d,J=12.2Hz,9H),1.08(d,J=12.8Hz,9H).

[0069] 13 C NMR (101MHz, CDCl3) δ139.07,137.47,137.35,133.97,133.95,130.50,129.78,129.75,127.09,126.46,126.20,125 .52,122.13,34.20,33.92,33.68,33.63,32.41,32.13,28.23,28.21,28.04,23.85,20.50,20.46,20.04,19.67.

[0070] 31 P NMR (162MHz,CDCl3)δ49.80-49.31.

[0071] 11 B NMR (128MHz, CDCl3)δ-41.92,-42.38,-43.21.

[0072] HRMS(ESI) Calculation for [M+Na,C 25 H 38 BNaP] + :403.2702,found:403.2701.

[0073] Example 2: Synthesis of 2,3-bis(o-phenylphenyl)cyclopropyldi-tert-butylphosphine borane adduct II-b

[0074] The difference from Example 1 is that (E)-1,2-di-o-methylstyrene is replaced by (E)-1,2-di-o-phenylstyrene

[0075] After the synthesis in step 1, 2,3-di(o-phenylphenyl)-1,1-dibromocyclopropane III-b is obtained:

[0076]

[0077] White solid, yield 88%, melting point: 243-244°C.

[0078] 1 H NMR (400MHz, CDCl3) δ7.45(m,8H),7.35(m,6H),7.26(m,2H),7.03(d,J=7.8Hz,2H),3.09(s,2H).

[0079] 13 C NMR (101MHz, CDCl3) δ144.13,140.83,133.67,130.15,129.94,128.43,127.82,127.62,127.47,127.25,41.71,38.95.

[0080] HRMS(ESI) Calculate for [M+H,C 27 H 22 Br2] + :503.0010,found:503.0008.

[0081] After the synthesis in step 2, 2,3-di(o-phenylphenyl)-1-bromocyclopropane IV-b is obtained:

[0082]

[0083] Yellow liquid, yield 59%.

[0084] 1 H NMR (400MHz, CDCl3) δ7.32–7.12(m,20H),6.89–6.83(m,2H),3.19(dd,J=7.9,4.3Hz,1H),2.75(dd,J=7.5,4.3Hz,1H),2.41(t,J=7.7Hz,1H).

[0085] 13 C NMR(101MHz, CDCl3) δ143.76,142.90,141.44,140.93,136.79,133.69,130.10,129.97,129.69,129.61,1 28.40,128.19,128.01,127.68,127.25,127.09,126.99,126.86,126.74,125.31,33.09,31.46,30.58.

[0086] HRMS(ESI) Calculate for [M+H,C 27 H 22 Br] + :425.0905,found:425.0906.

[0087] After the synthesis in step 3, 2,3-di(o-phenylphenyl)cyclopropyl di-tert-butylphosphine borane adduct II-b is obtained:

[0088]

[0089] White solid, yield 71%, melting point: 186-188°C.

[0090] 1 H NMR (400MHz, CDCl3) δ7.43–7.19(m,16H),7.11(dd,J=5.3,3.3Hz,1H),6.81(d,J=7.7Hz,1H),3.35(dt,J=11.9,7.3Hz, 1H),2.98(dt,J=9.6,7.5Hz,1H),1.55(ddd,J=9.6,7.2,5.3Hz,1H),1.04(d,J=12.2Hz,9H),0.94(d,J=12.8Hz,9H).

[0091] 13 C NMR (101MHz, CDCl3) δ143.34,143.26,141.90,140.69,138.10,132.61,132.58,130.12,129.97,129.95,129.84,128.37,128.23,127.91,127 .49,126.94,126.85,126.71,125.87,122.04,33.96,33.68,33.39,3 3.34,32.40,32.12,28.20,28.18,27.90,25.06,21.26,21.11,20.90.

[0092] 31 P NMR(162MHz,CDCl3)δ48.2,48.7.

[0093] 11 B NMR (128MHz,CDCl3)δ-41.3.

[0094] HRMS(ESI) Calculation for [M+Na,C 35 H 42 BNaP] + :527.3015,found:527.3015.

[0095] Example 3: Synthesis of 2,3-bis(o-methoxyphenyl)cyclopropyldi-tert-butylphosphine borane adduct II-c

[0096] The difference from Example 1 is that (E)-1,2-di-o-methylstyrene is replaced by (E)-1,2-di-o-methoxystyrene

[0097] After the synthesis in step 1, 2,3-di(o-methoxyphenyl)-1,1-dibromocyclopropane III-c is obtained:

[0098]

[0099] White solid, yield 51%, melting point: 172-173°C.

[0100] 1 H NMR (400MHz, CDCl3) δ7.30–7.28(m,2H),7.25–7.21(m,2H),7.20–7.16(m,2H),7.11(m,2H),4.00(s,6H)3.29(s,2H).

[0101] 13 C NMR (101MHz, CDCl3) δ143.29,140.64,138.08,132.53,130.08,129.94,52.33,52.11,33.35,33.29,32.36,21.22,20.86.

[0103] HRMS(ESI) Calculation for [M+Na,C 17 H 17 Br2O2] + :410.9595,found:410.9597.

[0104] After the synthesis in step 2, 2,3-di(o-methoxyphenyl)cyclopropyldi-tert-butylphosphine borane adduct IV-c is obtained:

[0105]

[0106] White liquid, yield 47%.

[0107] 1 H NMR (400MHz, CDCl3)δ7.29–7.26(m,2H),7.24–7.21(m,2H),7.18–7.16(m,2H),7.1 4(m,2H),4.02(s,6H)3.51(dd,J=7.8,4.5,1H),2.73(m,1H),2.63–2.60(m,1H).

[0108] 13 C NMR (101MHz, CDCl3) δ136.53,136.41,135.68,135.21,131.42,131.11,129.2 1,128.89,127.13,126.58,126.43,126.01,50.3,50.1,31.3,30.7,30.1.

[0109] HRMS(ESI) Calculate for [M+H,C 17 H 18 BrO2] + :333.0490,found:333.0491.

[0110] After the synthesis in step 3, 2,3-di(o-methoxyphenyl)cyclopropyldi-tert-butylphosphine borane adduct II-c is obtained:

[0111]

[0112] White solid, yield 51%, melting point: 172-173°C.

[0113] 1 H NMR (400MHz, CDCl3) δ7.46(ddd,J=14.5,7.6,1.7Hz,2H),7.32–7.17(m,2H),7.05–6.97(m,2H),3.87(s,3H),3.81(s,3H),3.51(d t,J=12.1,7.5Hz,1H),2.71(dt,J=9.5,7.1Hz,1H),1.58(dt,J=9.5,7.1,1H),1.12(d,J=12.4Hz,9H),1.03(d,J=12.6Hz,9H).

[0114] 13 C NMR(101MHz, CDCl3) δ159.29,128.95,128.61,125.72,120.22,110.45,77.35,7 6.72,55.85,37.96,36.10,35.93,35.70,27.93,27.77,27.08,26.71,25.75.

[0115] 31 P NMR (162MHz,CDCl3)δ49.5,49.9

[0116] 11 B NMR (128MHz,CDCl3)δ-44.1.

[0117] HRMS(ESI) Calculation for [M+Na,C 25 H 38 BNaO2P] + :425.2600,found:425.2599.

[0118] Embodiment 4:

[0119] Synthesis of 2,3-bis(o-methylphenyl)cyclopropyldi-tert-butylphosphine borane adduct II-d:

[0120]

[0121] The reactant IV-a (300 mg, 1 mmol) was weighed into a 50 mL Schlenk bottle equipped with electromagnetic stirring, dissolved in anhydrous tetrahydrofuran under an argon atmosphere, and n-BuLi in n-hexane solution (0.5 mL, 2.5 M, 1.2 mmol) was added dropwise at -100 ° C, and stirred at low temperature for 1 hour. Redistilled PPh2Cl (441 mg, 2 mmol) was added, and the reaction system was naturally warmed to room temperature and stirred for 4 hours. After the reaction was completed by TLC monitoring, the temperature was controlled in an ice-water bath (0 ° C), methanol was added dropwise to quench the reaction system, and 10 mL of ethyl acetate was extracted three times, the organic phases were combined, dried with anhydrous MgSO4, filtered, and the filtrate was concentrated by rotary evaporation. The crude product was separated by silica gel column chromatography (eluent: petroleum ether ~ petroleum ether / ethyl acetate = 100: 1) to obtain the target product II-d as a white solid with a yield of 71% and a melting point of 102-103 ° C.

[0122] 1 H NMR (400MHz, CDCl3) δ7.37(td,J=7.2,6.8,3.0Hz,2H),7.33–7.14(m,16H),2.97–2.82(m,2H),2.49(s,3H),2.41(s,3H),2.07(dt,J=8.8,6.0Hz,1H).

[0123] 13 C NMR (101MHz, CDCl3) δ141.29,139.47,139.37,139.14,139.04,138.25,138.19,133.09,132.90,132.71,132.53,129.22,129.19,128.67 ,128.57,128.50,128.44,128.36,128.29,128.06,126.65,126.59,126.37,40.12,39.87,32.41,32.35,29.92,29.84,29.48,29.35.

[0124] 31 P NMR (162MHz,CDCl3)δ-16.21.

[0125] HRMS(ESI) Calculation for [M+Na,C 29 H 37 BNaP] + :429.1748,found:429.1744.

[0126] Example 5: Application of cyclopropane skeleton monophosphine ligand in palladium-catalyzed CN bond coupling reaction

[0127]

[0128] In a glove box filled with argon, diphenylamine (0.17 g, 1 mmol), bromobenzene (0.17 g, 1.1 mmol), sodium tert-butoxide (0.13 g, 1.3 mmol), and toluene (2 mL) were added to the inner tube of a 10 mL autoclave, followed by the prepared palladium precursor toluene solution (1 mg / mL) and the ligand toluene solution (1 mg / mL), which were then sealed and taken out, loaded into the autoclave, replaced with an argon atmosphere, and stirred at 110 ° C for 24 hours. After the reaction was completed, the reaction solution was filtered through a dropper column, the filtrate was concentrated by rotary evaporation, and n-tridecane was added as an internal standard, and the yield and conversion rate were calculated using GC.

[0129] Table 1: Experimental results of palladium-catalyzed CN coupling reactions with different monophosphine ligands

[0130]

[0131] a The conversion rate and yield were determined by GC.

[0132] It can be seen from the data in Table 1 that compared with the biphenyl skeleton ligands JohnPhos and RuPhos, T-Phos has a higher conversion number and its catalytic activity is better than that of the biphenyl skeleton ligand.

[0133] Example 6: Cyclopropane skeleton monophosphine ligand regulated CN bond coupling reaction under different palladium precursors

[0134]

[0135] In a glove box filled with argon, diphenylamine (0.17 g, 1 mmol), bromobenzene (0.17 g, 1.1 mmol), sodium tert-butoxide (0.13 g, 1.3 mmol), and toluene (2 mL) were added to the inner tube of a 10 mL autoclave, followed by the prepared palladium precursor toluene solution (1 mg / mL) and the toluene solution of ligand II-a (1 mg / mL), which was then sealed and taken out, loaded into the autoclave, replaced with an argon atmosphere, and stirred at 110 ° C for 24 hours. After the reaction was completed, the reaction solution was filtered through a dropper column, the filtrate was concentrated by rotary evaporation, and n-tridecane was added as an internal standard, and the yield and conversion rate were calculated using GC.

[0136] Table 2: Experimental results of coupling of bromobenzene and diphenylamine regulated by cyclopropane skeleton monophosphine ligand under different palladium precursors

[0137]

[0138] a The conversion rate and yield were determined by GC.

[0139] From the data in Table 2, it can be seen that the highest conversion number can be obtained by using [(allyl)PdCl]2 as the catalyst precursor, so it is used as the optimal catalyst precursor.

[0140] Example 7: Effects of different solvents and bases on palladium-catalyzed CN bond coupling reactions

[0141]

[0142] In a glove box filled with argon, diphenylamine (0.17 g, 1 mmol), bromobenzene (0.17 g, 1.1 mmol), base (1.3 mmol), solvent (2 mL) were added to the inner tube of a 10 mL autoclave, and then the prepared palladium precursor toluene solution (1 mg / mL) and II-a toluene solution (1 mg / mL) were added, and the autoclave was sealed and taken out, replaced with an argon atmosphere and stirred at 110 ° C for 24 hours. After the reaction was completed, the reaction solution was filtered through a dropper column, the filtrate was concentrated by rotary evaporation, and n-tridecane was added as an internal standard, and the yield and conversion rate were calculated using GC.

[0143] Table 3: Experimental results of palladium-catalyzed CN coupling reactions under different monophosphine ligands

[0144]

[0145] a The conversion rate and yield were determined by GC. b ND means no product detected.

[0146] From the data in Table 3, it can be seen that the use of tert-butoxide as a base has the best effect. As the alkalinity increases, the conversion number decreases, and sodium tert-butoxide is selected as the optimal base. Coordinating solvents such as acetonitrile and tetrahydrofuran will greatly reduce the reaction activity. Using toluene as a solvent has the highest conversion number.

[0147] Example 8: Application of cyclopropane skeleton monophosphine ligand in palladium-catalyzed Suzuki coupling reaction

[0148]

[0149] In a glove box filled with argon, p-methyl bromide (0.17 g, 1 mmol), sodium phosphate (0.33 g, 2 mmol), phenylboric acid (0.14 mg, 1.1 mmol) were added to a 25 mL Schlenk tube, followed by a toluene solution of palladium acetate (1 mL, 0.1 μmol / mL) and a toluene solution of the ligand (1 mL, 0.2 μmol / mL), which was then plugged with a rubber stopper and taken out, and degassed water (1 mL) was added and stirred at 110°C for 2 hours. After the reaction was completed, the reaction solution was filtered through a dropper column, the filtrate was concentrated by rotary evaporation, and n-tridecane was added as an internal standard, and the yield and conversion rate were calculated using GC.

[0150] Table 4: Experimental results of palladium-catalyzed Suzuki coupling reaction under different monophosphine ligands

[0151]

[0152]

[0153] a The conversion rate and yield were determined by GC. b Reaction 6 hours

[0154] It can be seen from the data in Table 4 that compared with the biphenyl skeleton ligands JohnPhos and RuPhos, T-Phos has a higher conversion number and its catalytic activity is better than that of the biphenyl skeleton ligand.

[0155] Example 9: Application of cyclopropane skeleton monophosphine ligand in palladium-catalyzed Suzuki coupling reaction

[0156]

[0157] In a glove box filled with argon, p-methyl bromobenzene (0.17 g, 1 mmol), sodium phosphate (0.33 g, 2 mmol), phenylboric acid (0.14 mg, 1.1 mmol) were added to a 25 mL Schlenk tube, followed by a toluene solution of a palladium precursor (1 mL, 0.1 μmol / mL) and a toluene solution of ligand II-a (1 mL, 0.2 μmol / mL), which was then plugged with a rubber stopper and taken out, degassed water (1 mL) was added and stirred at 110°C for 2 hours. After the reaction was completed, the reaction solution was filtered through a dropper column, the filtrate was concentrated by rotary evaporation, and n-tridecane was added as an internal standard, and the yield and conversion rate were calculated using GC.

[0158] Table 5: Experimental results of Suzuki coupling reaction regulated by cyclopropane skeleton monophosphine ligand under different palladium precursors

[0159]

[0160] a The conversion rate and yield were determined by GC.

[0161] From the data in Table 5, it can be seen that the highest conversion number can be obtained by using Pd(OAc)2 as the catalyst precursor, so it is used as the optimal catalyst precursor.

[0162] Example 10: Suzuki coupling reaction regulated by cyclopropane skeleton monophosphine ligand under different bases and solvents

[0163]

[0164] In a glove box filled with argon, p-methyl bromide (0.17 g, 1 mmol), base (0.33 g, 2 mmol), phenylboronic acid (0.14 mg, 1.1 mmol) were added to a 25 mL Schlenk tube, followed by palladium precursor solution (1 mL, 0.1 μmol / mL) and ligand II-a solution (1 mL, 0.2 μmol / mL), which was then plugged with a rubber stopper and taken out, degassed water (1 mL) was added and stirred at 110°C for 2 hours. After the reaction was completed, the reaction solution was filtered through a dropper column, the filtrate was concentrated by rotary evaporation, and n-tridecane was added as an internal standard, and the yield and conversion rate were calculated using GC.

[0165] Table 6: Experimental results of coupling of bromobenzene and diphenylamine regulated by cyclopropane skeleton monophosphine ligand under different palladium precursors

[0166]

[0167] a The conversion rate and yield were determined by GC.

[0168] From the data in Table 6, it can be seen that using sodium phosphate as a base has the best effect; coordinating solvents such as acetonitrile and tetrahydrofuran will greatly reduce the reaction activity, and using toluene as a solvent has the highest conversion number.

[0169] The above description is only a preferred embodiment of the present invention. It should be pointed out that a person skilled in the art can make several modifications and improvements without departing from the inventive concept, which all belong to the protection scope of the present invention.

Claims

1. A cyclopropane skeleton monophosphine ligand having the following structural formula: in: R 1 is phenyl, substituted phenyl, C1-C8 alkyl, C1-C8 alkoxy, R 2 is phenyl, substituted phenyl, C1-C8 alkyl, R 1 , R 2 Same or different; The substituents in the substituted phenyl are one or more of C1-C8 alkyl, C1-C8 alkoxy, C2-C8 acyloxy, hydroxyl, halogen, amino, (C1-C8 acyl)amino, di(C1-C8 alkyl)amino, C1-C8 acyl, C2-C8 ester, and alkyl halide; the number of substituents is 0-5.

2. The cyclopropane skeleton monophosphine ligand according to claim 1, characterized in that R 1 It is C1-C4 alkyl or C1-C4 alkoxy.

3. The cyclopropane skeleton monophosphine ligand according to claim 2, characterized in that: R 1 It is methyl or methoxy.

4. The cyclopropane skeleton monophosphine ligand according to claim 1, characterized in that: R 2 It is a C1-C4 alkyl group.

5. The cyclopropane skeleton monophosphine ligand according to claim 4, characterized in that: R 2 It is tert-butyl.

6. A borane adduct of a cyclopropane skeleton monophosphine ligand prepared from the cyclopropane skeleton monophosphine ligand according to claim 1, characterized in that: It has the following structural formula:

7. A method for preparing the cyclopropane skeleton monophosphine ligand according to claim 1, characterized in that: Here are the steps: (1) Using 1-10 equivalents of base and 0.1-0.5 equivalents of TEBAC phase transfer catalyst, trans-1,2-diarylethene and solvent amount of bromoform are subjected to cyclopropanation reaction to prepare gem-dibromocyclopropane intermediate III, the reaction formula of which is: (2) In a mixed solvent of tetrahydrofuran and diethyl ether, 1-2 equivalents of LiBr are used as an additive, and 1-1.5 equivalents of n-butyl lithium are exchanged with the gem-dibromocyclopropane intermediate III at -78°C to -100°C. After the reaction is complete, the monobromocyclopropane intermediate IV is prepared by quenching with methanol. The reaction formula is: (3) In tetrahydrofuran, 1-1.5 equivalents of n-butyl lithium are exchanged with monobromocyclopropane intermediate IV at -78°C to -100°C. After the reaction is completed, 2-4 equivalents of PR are added. 2 2Cl, the system is naturally heated to room temperature and then stirred until the reaction is complete to obtain cyclopropane monophosphine ligand I, the reaction formula of which is:

8. An application of the complex of the cyclopropane skeleton monophosphine ligand and palladium as claimed in claim 1 as a catalyst to promote CN coupling reaction, wherein the reaction formula is: in: Ar 1 is phenyl, substituted phenyl, heteroaryl, or alkenyl; R 3 and R 4 is phenyl, substituted phenyl, C1-C8 alkyl, R 3 , R 4 are the same or different, and X is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

9. An application of the complex of the cyclopropane skeleton monophosphine ligand and palladium as claimed in claim 1 as a catalyst to promote Suzuki coupling reaction, wherein the reaction formula is: in: Ar 2 ,Ar 3 is phenyl, substituted phenyl, heteroaryl, alkenyl, Ar 2 ,Ar 3 They may be the same or different, and X is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

10. The use according to claim 9 or 10, characterized in that Ar 1 , R 3 , R 4 All are phenyl, X is Br; Ar 2 It is a phenyl group substituted with a methyl group at the para position.

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